7-103498280-TAAAAA-TA

Variant names:

• chr7-103498280-TAAAA-T
• rs745709647
• NM_005045.4:c.8668-32_8668-29delTTTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.8668-32_8668-29delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,600,952 control chromosomes in the GnomAD database, including 15,299 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.10 (1025 hom., cov: 31)
  • Exomes 𝑓: 0.13 (14274 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.463
• Publications: 0 publications found

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-103498280-TAAAA-T is Benign according to our data. Variant chr7-103498280-TAAAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.8668-32_8668-29delTTTT		intron_variant	Intron 53 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.8668-32_8668-29delTTTT		intron_variant	Intron 53 of 63		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1366-6120_1366-6117delAAAA		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.8668-32_8668-29delTTTT		intron_variant	Intron 53 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15540 AN: 151952 Hom.: 1026 Cov.: 31

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.104 AC: 26133 AN: 250102 AF XY: 0.106

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.0731

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.133 AC: 192196 AN: 1448882 Hom.: 14274 AF XY: 0.130 AC XY: 94132 AN XY: 721666

African (AFR) AF: 0.0224 AC: 744 AN: 33216

American (AMR) AF: 0.0782 AC: 3496 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3326 AN: 26054

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39614

South Asian (SAS) AF: 0.0511 AC: 4392 AN: 85990

European-Finnish (FIN) AF: 0.137 AC: 7330 AN: 53358

Middle Eastern (MID) AF: 0.125 AC: 715 AN: 5736

European-Non Finnish (NFE) AF: 0.150 AC: 164942 AN: 1100286

Other (OTH) AF: 0.121 AC: 7247 AN: 59950

GnomAD4 genome AF: 0.102 AC: 15534 AN: 152070 Hom.: 1025 Cov.: 31 AF XY: 0.100 AC XY: 7460 AN XY: 74334

African (AFR) AF: 0.0273 AC: 1131 AN: 41494

American (AMR) AF: 0.104 AC: 1590 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0474 AC: 229 AN: 4828

European-Finnish (FIN) AF: 0.150 AC: 1585 AN: 10558

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10066 AN: 67970

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.0745 Hom.: 119

Bravo AF: 0.0969

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46
BranchPoint Hunter		6.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745709647; hg19: chr7-103138727;